This invention relates to a method for immobilizing an anti-thrombogenic substance inside a macromolecular material bonded onto a base by photopolymerization, which is used as a base material of a medical device to be placed in contact with blood or to be inserted into a human or other animal body for use.
Various materials for imparting anti-thrombogenic or anticoagulant properties to the medical device have been researched and developed. Synthetic material having complete anti-thrombogenic or anticoagulant properties, however, has not been developed yet.
One approach for obtaining the anticoagulant properties has been studied. By this approach, an anticoagulant material is formed of heparin. Heparin devitalizes the blood coagulant system in vivo and biologically actively prevents the aggregation of platelets. Research and development has revealed the following major conventional methods for immobilizing heparin.
(1) A simple physical blending method. In this method, an aqueous solution of heparin and a solution of thermosetting resin are blended, applied to a surface of a base, and heated, thereby forming a membrane of thermosetting resin on the base. The membrane polymer is crosslinked by chemical reaction resulting from heating and is thereby caused to contain the heparin.
(2) An ionic bonding method. In this method, a blend or copolymer of a cationic substance in a polymer is immersed in a highly concentrated aqueous solution of heparin. By ionic bonding, heparin is immobilized in the blend or the copolymer.
(3) A covalent bonding method. In this method, a functional group or a bonding group R is introduced into heparin by applying a chemical modification of heparin. Heparin is immobilized on the surface of a base by a chemical reaction. Alternatively, by chemically modifying the surface of a base, the bonding group R is introduced. Such chemical modification causes heparin to be immobilized on the surface of the base.
The aforementioned methods, however, have the following problems, respectively.
In the physical blending method, the heparin is dispersed non-uniformly in a solvent. As a result, the prepared film is not uniform. Furthermore, since the thermosetting resin membrane is bonded onto the base with insufficient bonding force, the membrane gradually peels off from the base when the film is used in blood. Also, in the same way as in the ionic bonding method, heparin is easily discharged from the membrane. Therefore, the effect of the anti-thrombogenic properties of heparin can be expected for only a short time period.
In the covalent bonding method, the insolubility of heparin in the organic solvent restricts the chemical reaction. Moreover, since only a small quantity of heparin is bonded to the base, the anticoagulant properties are developed only for a very short time period.